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Biomedical subjects

A Stark

Publications and source records attributed to A Stark.

At least 55 records · Page 3Linked to original sources

Localization of three human polypeptide GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation throughout the Golgi apparatus.

O-glycosylation of proteins is initiated by a family of UDP-N-acetylgalactosamine:polypeptide N-acetylgalactos-aminyltransferases (GalNAc-T). In this study, we have localized endogenous and epitope-tagged human GalNAc-T1, -T2 and -T3 to the Golgi apparatus in HeLa cells by subcellular fractionation, immunofluorescence and immunoelectron microscopy. We show that all three GalNAc-transferases are concentrated about tenfold in Golgi stacks over Golgi associated tubular-vesicular membrane structures. Surprisingly, we find that GalNAc-T1, -T2 and -T3 are present throughout the Golgi stack suggesting that initiation of O-glycosylation may not be restricted to the cis Golgi, but occur at multiple sites within the Golgi apparatus. GalNAc-T1 distributes evenly across the Golgi stack whereas GalNAc-T2 and -T3 reside preferentially on the trans side and in the medial part of the Golgi stack, respectively. Moreover, we have investigated the possibility of O-glycan initiation in pre-Golgi compartments such as the ER. We could not detect endogenous polypeptide GalNAc-transferase activity in the ER of HeLa cells, neither by subcellular fractionation nor by situ glycosylation of an ER-retained form of CD8 (CD8/E19). However, upon relocation of chimeric GalNAc-T1 or -T2 to the ER, CD8/E19 is glycosylated with different efficiencies indicating that all components required for initiation of O-glycosylation are present in the ER except for polypeptide GalNAc-transferases.

Base Sequence↗

Reconstruction in metastatic destruction of the acetabulum. Support rings and arthroplasty in 12 patients.

In 12 patients with acetabular metastases, we reconstructed the hip with a support ring, cement, and Charnley prosthesis with a 22 mm head. There were no immediate postoperative deaths or cardiovascular complications. Dislocations occurred in 5 patients, 1 of whom required open reduction. At follow-up, 3 patients were alive 11, 15, and 18 months after surgery. 9 patients died after 8 (2-13) months. All patients obtained relief from pain, became ambulatory and were discharged to their homes. 1 patient had rapid disease progression with pathologic fracture and cranial dislocation of the support ring. Among the remaining 11 patients, the hip has not again caused pain or limited function. There were no signs of loosening, except in the patient with fracture of the hemipelvis. Remineralization was observed in 2 breast cancer patients after chemotherapy. Hip reconstruction can restore painless function until death in cancer patients with severe destruction of the acetabulum.

Acetabulum↗

Localization of the human soluble epoxide hydrolase gene (EPHX2) to chromosomal region 8p21-p12.

Epoxide hydrolases have an important function in organisms in that they catalyze the transformation of potentially toxic or carcinogenic epoxides into the corresponding diols. In this study, the chromosomal localization was determined for the human gene encoding soluble epoxide hydrolase. A polymerase chain reaction fragment corresponding to the C-terminal region of the mouse protein was used to isolate a cosmid clone from a human genomic library. By fluorescence in situ hybridization to metaphase chromosomes, the soluble epoxide hydrolase gene was then localized to chromosomal region 8p21-p12.

Animals↗

Mortality among New York State highway maintenance workers: 1958-1980.

The mortality profile of 9585 male New York State Department of Transportation (NYSDOT) highway maintenance workers was examined by calculating age-era standard mortality ratios (SMRs), using the general male population of upstate New York as a reference group, for the period 1958-1980. The SMR for all workers was 1.14 (95% CI = 1.09, 1.18), with the greatest all-cause mortality among laborers (SMR = 1.23, 95% CI = 1.16, 1.29). The major contributors to this increase among laborers were circulatory system diseases (SMR = 1.18, 95% CI = 1.10, 1.27), diseases of the respiratory system (SMR = 1.34, 95% CI = 1.09, 1.64), digestive system diseases (SMR = 1.57, 95% CI = 1.26, 1.94), genitourinary system diseases (SMR = 1.61, 95% CI = 1.02, 2.41) and accidents, poison, and violence (SMR = 1.44, 95% CI = 1.19, 1.74). Some of the elevated risks observed may be attributed to cigarette smoking and other life-style factors that could not be assessed with the data available. However, the mortality risks for laborers increased with length of employment and latency, suggesting that occupational exposures may be contributing to the elevated risk in this cohort. Further studies should include information on life-style variables and other confounders as well as more detail on specific occupational exposures.

Adult↗

Changes in intestinal tunica muscularis following dietary fiber feeding in rats. A morphometric study using image analysis.

The morphological changes in the intestinal tunica muscularis induced by prolonged dietary fiber intake were determined in rat small intestine and colon with the aid of computerized image analysis. Thirty male Sprague-Dawley rats were fed either a fiber free, 15% cellulose or 15% pectin diet for 8 weeks. Intestine length was measured and stained cross sections of the jejunum, ileum, and colon were quantitated using image analysis. In the distal colon, muscle cell size was also determined. Despite lower weight gain in the pectin fed rats, both the small intestine and colon length were significantly increased. Cellulose feeding had a lesser effect on intestine length. Pectin fed rats had significantly increased relative tunica muscularis area (37.2 +/- 2.2 mm2) in ileum cross sections when compared to control (24.3 +/- 1.8 mm2) and cellulose fed rats (26.1 +/- 1.1 mm2). In the mid-colon, the tunica muscularis area was found to be pectin > cellulose > control (33.5 +/- 2.2; 29.7 +/- 1.7; 25.8 +/- 1.5 respectively) with significant differences reached between pectin and control rats. In jejunal samples, no differences were observed among the groups. Circular smooth muscle cell size in the distal colon was significantly increased following cellulose feeding but was less pronounced in the case of pectin. We conclude that fiber supplementation leads to morphological changes in the rat intestine including changes in length and tunica muscularis volume.

Animals↗

Tissue specific basal expression of soluble murine epoxide hydrolase and effects of clofibrate on the mRNA levels in extrahepatic tissues and liver.

The soluble epoxide hydrolase mRNA level in liver was increased eight-fold upon administration of the hypolipidemic drug and peroxisome proliferator clofibrate for 7 days to mice. The soluble epoxide hydrolase mRNA was back at control levels within 1-2 days after clofibrate withdrawal. The highest expression was in liver, intestine and kidney. Lower levels were found in heart and muscle and very low levels were found in testes, lung, brain and spleen. The mRNA levels were increased in liver, kidney and heart by clofibrate.

Animal Feed↗

Neurotoxicity among pesticide applicators exposed to organophosphates.

OBJECTIVES: An epidemiological study of 90 male pesticide applicators licensed in New York was conducted to investigate the effect of exposure to organophosphate pesticides on the peripheral nervous system. METHODS: A cohort of farmers and pesticide applicators from New York State were questioned off season (November 1988-February 1989) and again during the spraying season (April 1989-August 1989) about the presence of several acute signs and symptoms. Short term exposure was validated by measuring the concentration of dimethylthiophosphate (DMTP), a metabolite of guthion, in urine. Chronic signs of subtle peripheral nerve damage were determined by vibration threshold sensitivity of the farmers and applicators tested during November 1988-February 1989 and compared with controls drawn from the general population who were tested during the same time period the next year (November 1989-February 1990). Vibration threshold sensitivity was determined for both the hands and feet. Long term exposure to pesticides was determined by questionnaire. RESULTS: Paired t tests show that mean vibration threshold scores were significantly higher for the dominant (P < 0.00) and non-dominant (P < 0.04) hands among pesticide applicators when compared with scores for population based controls individually matched on age, sex, and county of residence. CONCLUSIONS: A significant increase in mean vibration threshold sensitivity for the dominant and non-dominant hand suggests previous organophosphate exposure among pesticide applicators was associated with a loss of peripheral nerve function.

Adult↗

Evaluation of the impact of allogenic transplant in first remission on an unselected population of patients with acute myeloid leukaemia aged 15-55 years. The Northern Regional Haematology Group.

The aim of this study was to collect prospectively unselected, population-based data on young adults with acute myeloid leukaemia (AML) over a 9-year period and to evaluate the impact on survival of the introduction of allogeneic transplantation performed in first remission. The population within the Northern Region of England is 3.09 million. During the study period a total of 149 de novo patients between 15 and 55 years old presented. The incidence of AML was 0.79 per 10(5) (age-specific population) in the 15-24-year-old group, 0.85 per 10(5) in the group 25-39 years old and 1.35 per 10(5) in the 40-55-year-old group. Remission induction success varied with age (74% for patients < 40 years and 58% for patients 40-55 years). In the 15-40 year old group 28 patients had an HLA-matched donor, 22 patients had a transplant (one syngeneic) and 24 patients in the 15-40-year-old group in remission at 6 months did not have a transplant. The allogeneic group < 40 years old had an event-free survival (EFS) at 4 years of 62%, whereas patients of the same age who received chemotherapy alone had an EFS at 4 years of 24%. A small heterogeneous group of 14 patients who had intensification with autotransplant are not included in this analysis. The population study approach demonstrates the difficulties of introducing uniform treatment strategy in this disease group. The study confirms the view that allogeneic transplant in first remission in the 15-40-year-old group is the treatment of choice. Unfortunately the overall impact of transplant on the population is not great since only 22 of 149 patients (14%) were able to receive an allograft in first remission.

Adolescent↗

Late follow-up results of operative ankle arthroscopy in patients under local anaesthesia.

The purpose of this study was to evaluate our long-term results of operative ankle arthroscopy in local anaesthesia, without tourniquet and antibiotic prophylaxis, and to see whether we could produce the same results other investigators had published using general anaesthesia. Between 1987 and 1992, 51 operative ankle arthroscopies were performed--all as out-patient procedures. Thirty-six patients had local anaesthesia, 7 had general anaesthesia, one had spinal anaesthesia and one had epidural anaesthesia. No prophylactic antibiotics were given. Indications for surgery were the same for patients who had local anaesthesia as for those who had the other types of anaesthesia. Nineteen patients had partial synovectomies, 8 had removals of osteophytes, 7 had debridements of osteochondral fractures, 6 had debridements of mild degenerative osteoarthritis, 3 had loose bodies and 2 had septic arthritis. After a mean of 3 years (range 1-8) the patients were sent a questionnaire. They were asked to rate activity level, pain, swelling, and limb stiffness on a four-grade scale pre- and postoperatively and to rate their total subjective improvement. They were also asked if they would undergo the same procedure again knowing the outcome of the procedure. Forty-five patients (88%) were available for follow-up. Thirty-four patients (76%) were improved, 10 remained unchanged, and one became worse after surgery. No correlation existed between preoperative symptom duration, sex, trauma, type of anaesthesia, postoperative diagnosis or type of surgical procedure. Minor complications occurred in 11% of patients. Eighty-four percent of the patients said they would undergo the same procedure again. The type of anaesthesia used did not influence this decision.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Purification and characterization of multifunctional enzyme from mouse liver peroxisomes.

A simple and rapid purification procedure for hepatic peroxisomal multifunctional enzyme (delta 3, delta 2-enoyl-CoA isomerase/enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase) from clofibrate treated mice is described. The purification is achieved within two days using ion-exchange chromatography and an easily prepared affinity resin. The overall yield is 10% or more after a 100-fold enrichment from the cytosolic fraction of liver tissue. The native enzyme is a monomer with a molecular mass of 75 kDa. The protein is blocked in the N-terminus but internal amino acid sequences was obtained after proteolytic cleavage. Western blot analysis indicated proteolysis of multifunctional enzyme in different subcellular fractions derived from liver tissue. The hydratase activity of the enzyme is heat-labile and highly dependent on the concentration of Tris buffer or potassium chloride present. Optimal activity was found around 37 degrees C and pH 7. The enzyme also shows dehydrogenase and isomerase activity.

3-Hydroxyacyl CoA Dehydrogenases↗

Malignant mesothelioma: attributable risk of asbestos exposure.

OBJECTIVES: To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin. METHODS: Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals. Cases whose diagnosis was confirmed in a special pathology review as definite or probable mesothelioma (n = 208) were included in the analysis. Controls (n = 533) had died of other causes, excluding cancer, respiratory disease, suicide, or violence. Direct exposure to asbestos was determined from responses to three types of questions: specific queries as to any exposure to asbestos; occupational or non-vocational participation in any of nine specific activities thought to entail exposure to asbestos; and analysis of life-time work histories. Indirect exposures were assessed through residential histories and reported contact with family members exposed to asbestos. RESULTS: Among men with pleural mesothelioma the attributable risk (AR) for exposure to asbestos was 88% (95% confidence interval (95% CI) 76-95%). For men, the AR of peritoneal cancer was 58% (95% CI 20-89%). For women (both sites combined), the AR was 23% (95% CI 3-72%). The large differences in AR by sex are compatible with the explanations: a lower background incidence rate in women, lower exposure to asbestos, and greater misclassification among women. CONCLUSIONS: Most of the pleural and peritoneal mesotheliomas in the men studied were attributable to exposure to asbestos. The situation in women was less definitive.

Adult↗

[Prosthesis replacement in the hip joint in prosthesis fracture. Clinical and radiological results after 5 years].

The results of 45 revisions performed for fracture of the femoral stem in patients with total hip replacements were reviewed after an average follow-up time of 5 (3-7) years. We were able to examine 38 of the patients. Surgery was performed in a standardized way through a posterior approach and with a dorsal proximal window in the femur. In 7 cases the femoral stem only was changed, while in 31 both components had to be replaced. The femoral components implanted were of the revision type, and were cemented and individually selected in each case. To stabilize large acetabular defects a combination of an acetabular support ring and a homologous bone graft was used in 21 cases; bank bone was used in a total of 28 hips. During surgery 1 fracture and 4 defects of the femur occurred. Good intraoperative stability of the femoral component was attained in every case, allowing full weight-bearing during mobilization unless acetabular instability was present. There were no deep infections. One dislocation had to be treated by closed reduction. Clinical evaluation was performed according to Merle d'Aubigné. Radiological loosening was classified according to Gruen, DeLee and Charnley. Clinical results were good in 33 (87%) and were rated as poor in 5. In the latter group a good correlation between subjective and objective parameters was noted in 4 of the 5 patients. Two acetabular and two femoral components in 3 patients were classified as radiologically loose; in 1 of these the cup was not changed at revision.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats.

The hypocholesterolaemic properties of an ethanol extract from defatted fenugreek (Trigonella foenum-graecum) seeds were investigated. Purification of the crude extract by dialysis produced an isolated component with haemolytic properties. The dialysate was also found to contain saponins demonstrated by thin-layer chromatography. Experiments in vitro employing the everted-sac technique showed that the ethanol extract had the ability to inhibit taurocholate and deoxycholate absorption in a dose-dependent manner. In two separate feeding experiments, hypercholesterolaemic rats were fed on 30 or 50 g ethanol extract/kg for a 4-week period. Reductions in plasma cholesterol levels ranged from 18 to 26% and a tendency for lower concentrations of liver cholesterol was observed. These results indicate that the ethanol extract from fenugreek seeds contained hypocholesterolaemic components which appear to be saponins that interact with bile salts in the digestive tract.

Animals↗

Healing complications after internal fixation of trochanteric hip fractures: the prognostic value of osteoporosis.

In a 3-year prospective randomized trial, the prognostic value of osteoporosis in terms of predicting healing complications due to implant failures or loss of fracture reduction has been studied in 113 patients with inter-trochanteric hip fractures treated with either a sliding screwplate or Ender nailing. According to the Barnet and Nordin's osteoporosis index, 66 patients were considered to have moderate or severe osteoporosis. There were no differences between patients with or without osteoporosis as regards the number of fractures with collapse in varus > 10 degrees, redislocation > 10 mm, or compression exceeding 10 mm. Six months after surgery, 48 patients failed in healing or healed with complications. These cases disclosed increased osteoporosis in comparison with those showing noncomplicated healing. Patients with osteoporosis who had unstable fractures treated by Ender nailing were found to have the worst prognosis for healing complications (p = 0.006). Of the 33 fractures with implant failures, 25 (76%) occurred in patients with osteoporosis (p = 0.04). In patients with osteoporosis, the frequency of mechanical failures was significantly higher in fractures with the device positioned incorrectly. Independently of the device used, patients with unstable trochanteric hip fractures and osteoporotic bone were the group with the highest risk for failures of the implant.

Aged↗